A novel proprioceptive rehabilitation program: A pilot randomized controlled trail as an approach to address proprioceptive deficits in patients with diabetic polyneuropathy

Background Diabetic polyneuropathy (DPN) is a notable microvascular complication of DM, affecting 16%-66% globally. DPN often leads to proprioceptive deficits in the lower limbs (LL), leading to impaired functional performance. However, evidence supporting proprioceptive rehabilitation programs (PRP) for DPN remains scarce. Aims This pilot study aims to evaluate the effectiveness of a novel 12-week PRP on LL static and dynamic proprioception and shed light on the potential benefits of PRP for DPN population. Methods Randomized Controlled Trail was conducted among 30 DPN patients (age 53.25±7.72 years, BMI 24.01±1.41 and DM duration 9.48±6.45 years), randomly allocated to intervention (n = 15) or control (n = 15) groups. The intervention group received PRP 3 times/week for 12 weeks. The control group received no exercise. Both groups received regular diabetic care. Static and dynamic proprioception of both LL were assessed at baseline, 6 weeks and 12 weeks. Position-reposition test was used to assess ankle joint position sense by obtaining difference between target and reproduced angles. Error in detecting knee angle and speed were obtained by performing Lower Limb Matching and Sense of Movement tests respectively to assess dynamic proprioception. Results Two-way ANOVA and paired comparisons revealed, no significant improvement in proprioceptive deficits at 6 weeks (p>0.05), but significant improvement was achieved at 12-weeks (p<0.05) in the intervention group. Mean errors in Pposition re-position(R:p<0.001, L;p<0.001) and Lower limb matching (R:p<0.001, L;p<0.001) tests reduced by 5° and 10° respectively, indicating a70% improvement in the intervention group. Error of detecting speed reduced only on right side by 0.041ms-1 accounting for a 42% improvement. No improvements were observed in the control group. Conclusions Novel 12-week PRP may yield a significant reduction in LL proprioceptive deficits among DPN patients. Future RCTs with larger samples should compare the effectiveness of this PRP compared with conventional rehabilitation programs.


Exclusion Criteria
 Patients with a history of cardiovascular diseases, recent surgery, severe pain and paresthesia, other types of neuropathy, diabetic foot ulcers, impaired vision, autonomic dysfunctions, significant psychiatric disorders, amputation, pregnant women, and obese patients  Patients and who were not willing to give consent were excluded

Sampling Method
An unbiased sample of thirty patients was obtained from the patients who regularly visited Diabetic and Endocrinology Clinic.The selected patients randomly allocated either to the intervention group (n=15) and control group (n=15) using concealed envelop randomization.
For this randomization, the random allocation sequence was generated and it remained concealed in sequentially numbered, opaque envelopes which were assignment sealed.Patient drew a number in sequence and patient's reference number was noted on the envelope before tearing it.Lastly, the envelop was opened to disclose the treatment allocation.The patient and the assessor were blind from group allocation.Neuropathy Screening Instrument (MNSI). 1,2During the screening, the self-administered questionnaire (Part A) of MNSI was distributed among the patients who were at the clinic.

Variables
Patients with DPN symptoms who scored greater than 4 in the self-administered questionnaire of MNSI were selected. 3,4,5Then, the physical examination part (Part B) of the MNSI was conducted among the selected patients to confirm the presence of DPN.Patients who scored greater than 2 points in the physical assessment part of MNSI were diagnosed with DPN and hence recruited to the study. 1,3,6This method was applied to the pre-defined group until the required study sample of 30 patients was fulfilled.
After obtaining informed written consent from the eligible participants, demographic data i.e., age, sex, type and duration of diabetes were recorded.Then, the participants were randomly allocated into either the intervention group (n=15) or the control group (n=15).
This study was designed to assess the efficacy of a specially designed, evidence-based, novel proprioceptive rehabilitation program (PRP) in improving static and dynamic proprioception in lower limbs compared to no intervention in patients with DPN.Intervention group underwent PRP for 45 minutes of duration, thrice a week for 12 weeks.The control group received no exercises.Both groups had regular diabetic care and attended the clinic continuously.Participants who were unable to follow the program continuously for more than three consecutive weeks were disqualified from being a subject in the study.Proprioception of both the lower limbs was assessed by static and dynamic proprioception functions 1,7 at the baseline, at the 6 th week (mid-assessment) and at the 12 th week (post-test assessment) by an independent assessor who was blind to the group allocation.

Outcomes of interest and outcome measuring tools:
 Position-reposition test to assess the static position sense at ankle joint

Measurement of Static Position Sense
'Position-reposition test' was used to evaluate the static position sense in both ankle joints which assessed the ability of the patient to match input from muscle and joint proprioceptors.
'Position-reposition test' was conducted as follows (Figure 1A): i. Participant seated in a high-sitting position on a wooden stool with eyes closed, the knees flexed at 90° and the lower leg positioned vertically.
ii. Participant's ankle joint was set to a pre-determined position of 30° of plantar flexion (target position) by the investigator.
iii.The position was held for 2-4 seconds by the investigator which allowed the participant to feel and remember the target position followed by passively moving the ankle into starting position.Participant was then instructed to reproduce the angle at the same ankle joint from the neutral position.

iv.
The difference between the target position and the reproduced position 8 was measured using goniometer in Kinovia movement analysis software to identify the accuracy of the static position sense (Figure 1B) v. Same procedure was repeated with second predetermined position of 10° of dorsiflexion to the same leg. vi.
Participant performed three trials in each leg and each trial was followed by 15-second rest period.The tests were conducted as follows : i. Participant seated in a high-sitting position on a wooden stool with eyes closed, the knees flexed at 90° and the lower leg positioned vertically.
ii. Investigator moved the participant's lower limb forward and backward (flexion and extension) in different speed and instructed the participant to follow the same movement with the contralateral leg at the same speed and same direction.
iii.The difference between target (ipsilateral) and reproduced (contralateral) knee joint angles were recorded to the nearest 0.01º degrees using Goniometer in Kinovia movement analysis software (Figure 2).

iv.
The mean difference between the target (ipsilateral) and reproduced (contralateral) knee angles in three trails were calculated to obtain the 'mean angle difference' as the outcome measure of the 'Lower Limb Matching Test' were designed to address the following key elements; participant's concentration, rationalization, feedback, active exercises, and repetitions to improve postural stability. 9,10,11,12  these elements act as adaptive codes to improve neuromuscular adaptation by recruiting proprioceptors to improve postural instability.
The progression of each exercise was carried out by modifying the movement parameters i.e.A proper warm-up and cool down sessions were conducted before and after each rehabilitation session to improve the effectiveness of the exercise program as well as to reduce the incidence of injuries.One session of the proprioceptive rehabilitation program was carried out for 40-45 minutes, 3 days per week for 12 weeks.
The rehabilitation protocol was devised to increase the difficulty of the exercises every 2 weeks throughout the designated 12-week period.As the training progressed, each exercise was modified to make them more demanding by removing visual feedback (eyes closed) and alteration the support surface, body position, direction, speed, and distance.

Statistical Analysis
Data from 30 participants from intervention group (n=15; 6 males, 9 females) and control group

Criteria
Having type-2 DM for one or more than one year  Diagnosed with DPN  Within the age group of 35-60 years  Provided informed written consent to participate in the study


Diabetic polyneuropathy  Lower Limb static and dynamic proprioception Data Collection and Data Collection Tools Ethical clearance for this study was obtained from Ethics Review Committee, Faculty of Medicine, University of Peradeniya (2023/EC/20), and it was registered under Sri Lanka Clinical Trial Registry with the registration number of SLCTR/2023/017 to conduct as a clinical trial.Patients were recruited from the Diabetic and Endocrinology Clinic at National Hospital Kandy in October 2023.One hundred and twenty patients with type-2 DM were screened using validated and reliability tested Sinhala and Tamil versions of Michigan


Lower limb matching test to assess the ability of the patient to perceive the knee joint movement  Sense of movement test' to assess the ability of the patient to perceive the lower limb movement Tests and Measurements: Static position sense and dynamic movement sense were assessed in both the legs to identify the lower limb proprioception function in each participant at the baseline, 6 weeks after the commencement of rehabilitation program and at the completion of 12-week rehabilitation program in intervention group and without any intervention in control group.Prior to each test, participant was familiarized with the particular tests by giving clear and accurate instructions and demonstrations.Visual and auditory cues were eliminated during proprioception assessments.

Figure 1
Figure 1 (A) Performing 'Position re-position' test to assess lower limb static proprioception.

Figure 2 .Figure 3 .
Figure 2. Measuring target angle and reproduced angle for 'Lower Limb Matching Test' force, length, velocity and endurance of each exercise.The exercise was further challenged by reducing base of support (BOS), increasing center of gravity (COG) sway on BOS, changing the surface on which the participant performs the exercises, engaging upper limb tasks while maintaining balance, introducing different obstacles in the walkway and removing visual cues by instructing the participant to perform some exercises with eyes closed.Closed kinetic chain exercises which were performed on the firm surface i.e. floor and foam surface i.e. cushion was designed to improve neuromuscular control of lower limb muscles through proprioceptors.Single leg standing exercises was designed to challenge the lower limb muscles and recruit the neuromuscular system for proximal stabilization at the hip, which was essential in maintaining postural stability during different tasks.Exercises designed to perform simultaneous activities of the upper limb while the participant balances on lower limbs helped to challenge the neuromuscular pathways by effectively engaging proprioceptors for motor control.Despite the included exercises resembled ordinary exercises, each component of the exercise designed and modified based on the basic concepts of improving impaired proprioception.

(
n=15; 4 males, 11 females) were included in the analysis.Absolute mean difference for position repositioning test, mean angle difference for lower limb matching test and mean speed difference for sense of movement tests were obtained at three-time points i.e., baseline, 6 weeks and 12 weeks were compared between the intervention and control groups to investigate the effectiveness of the novel proprioceptive rehabilitation program on proprioception compared to no intervention.Baseline data were compared between two groups to investigate the normality and homogeneity of variance across all the variables using Shapiro-Wilk test and Levene's test respectively.Two-way, group (intervention vs. control) × time (pre vs. post) repeated measure analysis of variance (ANOVA) was conducted on outcome measures related to static and dynamic proprioception to validate the novel proprioceptive rehabilitation program as a therapeutic tool to improve lower limb proprioception.Further, post-hoc analysis were performed to investigate whether the treatment duration i.e., 6 weeks and 12 weeks influence the improvement of lower limb proprioception.The level of significance was ascertained at a cut off p value of less than 0.05.All statistical analyses were performed using IBM SPSS 22.0 software (Armonk, NY: IBM Corp).with legs crossed and performed slow strokes over the anterior and posterior aspect of leg, in the distal to proximal direction using pads of the fingers (from the tip of the toes to knee) followed by circular kneading over the toes and foot using the pads of the thumbs (from the tip of the toes to ankle).to slowly move his/her ankle in an upwarddownward direction, clockwise and anticlockwise while sitting on a chair.to stand while bending the front leg and keeping the back leg straight.Then the patient was instructed to lean forward until he/she felt a stretch on calf muscles and keep that position for 30 sec and release.the same exercise on different platforms with eyes-closed, changed the direction, distance and speed of arm movements.Participant was sitting on a high couch and instructed to keep his/her ankle plantar flexed at 30⁰.Physiotherapist applied a force against the position and suddenly removed the hand and the participant was instructed to maintain the ankle in position at the same angle.
the leg in space in the direction of different numbers, shapes, letters of English alphabet, letters of Sinhala alphabet and clock times.Picked up a few objects (pen, small stone, piece of cloth, chalk, bottle lid) placed on the floor from the toes and put them into the box, one object at one time.Performed the exercise with eyes-closed.to stand while bending the front leg and keeping the back leg straight.Then the patient should lean forward until he/she feels a stretch in calf muscles.Participant should keep that position for 30 sec and release.